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Biomedical subjects

H Openshaw

Publications and source records attributed to H Openshaw.

At least 37 records · Page 2Linked to original sources
PubMed1995

Immune-mediated myelopathy after allogeneic marrow transplantation.

We describe two patients who developed myelopathy 15 and 27 months after allogeneic marrow transplantation. Exacerbations of the myelopathy occurred, with the development of optic neuropathy in one patient when corticosteroid therapy was tapered. The other patient had two exacerbations, 28 months and 40 months after transplantation, both of which resolved with plasma-pheresis. These case reports suggest that immune-mediated disease after transplantation can affect the central nervous system.

Adult↗
PubMed1992

Antiviral effects of herpes simplex virus specific anti-sense nucleic acids.

We have targeted mRNA sequences encompassing the translation initiation codon of the essential herpes simplex virus type 1 (HSV-1) IE3 gene with three kinds of anti-sense molecule. Addition of a 15mer oligodeoxyribonucleoside methylphosphonate to tissue culture cells resulted in suppression of viral replication. HSV-1 replication was also inhibited in cultured cells containing anti-sense vectors expressing transcripts complementary to the IE3 mRNA. We have also constructed a ribozyme which upon base pairing with the target IE3 mRNA induces cleavage at the predicted GUC site. A major obstacle to anti-sense studies in animals is drug delivery of preformed antisense molecules to ganglionic neurons, the site of HSV latency and reactivation. We speculate as to how this may be accomplished through carrier compounds which are taken up by nerve terminals and transported by retrograde axoplasmic flow. By the same route, HSV itself may be used as an anti-sense vector.

Animals↗
PubMed1991

Early loss of astrocytes in herpes simplex virus-induced central nervous system demyelination.

Immunohistochemistry was used to study herpes simplex virus type 1-induced central nervous system demyelination in the trigeminal root entry zone of mice inoculated with herpes simplex virus type 1 by the corneal route. There was no change in peripheral nervous system myelin as shown by immunostaining for P0 glycoprotein. Double immunoperoxidase staining for herpes simplex virus type 1 antigens and glial fibrillary acidic protein showed that most of the infected cells were astrocytes. Glial fibrillary acidic protein immunostaining was completely lost in the inferior medial portion of the trigeminal root entry zone at 6 days after herpes simplex virus type 1 inoculation, a time when central nervous system myelin was preserved as indicated by immunostaining for myelin basic protein. The pattern of glial fibrillary acidic protein staining did not change and herpes simplex virus type 1 antigens were no longer detected after day 8. There was a progressive loss of myelin basic protein staining within the area unstained by glial fibrillary acidic protein antisera on days 8 to 14. This pattern of astrocyte loss before central nervous system demyelination is strikingly different from the reactive astrocytosis seen in other demyelinating lesions, such as acute experimental allergic encephalomyelitis, progressive multifocal leukoencephalopathy, or acute multiple sclerosis. Herpes simplex virus type 1 infection in mice provides an unusual model of acute central nervous system demyelination preceded by a loss of astrocytes.

Animals↗
PubMed1991

Application of polymerase chain reaction assays to studies of herpes simplex virus latency.

We have amplified herpes simplex virus type 1 (HSV-1) DNA sequences from individual latently infected mouse trigeminal ganglia by polymerase chain reaction (PCR) assays. This report presents two useful modifications in the PCR technique. The first involves the use of two sets of closely spaced, oppositely oriented oligonucleotide primers and two rounds of 20-40 PCR cycles, first with the more widely spaced outer primers and then with the internal nested primers. This method enhanced the sensitivity of PCR detection as shown by assays of HSV-1 sequences in human brain. The second modification was designed to detect selectively HSV-1 sense or anti-sense RNA transcripts when both are present by adding a single primer during an initial reverse-transcriptase-mediated cDNA synthesis reaction. After destruction of the RNA template, standard PCR is initiated by the addition of the second primer and thermus aquaticus DNA polymerase (Taq). We show here applications of both of these modifications to amplify HSV-1 sequences from nervous system tissue.

Base Sequence↗
PubMed1991

Detection of herpes simplex virus DNA sequences in corneal transplant recipients by polymerase chain reaction assays.

Polymerase chain reaction (PCR) assays were used to amplify herpes simplex virus type 1 (HSV-1) thymidine kinase (TK) sequences in DNA extracted from formalin-fixed, paraffin embedded corneas of patients undergoing corneal transplantation. PCR reamplification with an internal (nested) set of primers was required for detection in 10 of the 12 positive corneas indicating very low abundance of viral sequences. Three of the positive corneal samples were from failed corneal grafts. Overall, TK sequences were detected in 8 of 11 corneas from subjects with a past history of herpes keratitis and in 4 of 11 corneas from subjects with no past history of herpetic eye disease.

Adult↗
PubMed1991

Ocular acyclovir delivery by collagen discs: a mouse model to screen anti-viral agents.

Discs 1.6 mm in diameter trephined from corneal collagen shields were used to deliver acyclovir (ACV) to the cornea of mice inoculated with herpes simplex virus type 1 (HSV-1). In the first minute after application to the cornea, there was a 23% decrease of ACV in the discs. After the first minute, ACV clearance from the discs appeared to be exponential with a half-life of 21 minutes. Treatment given 3 times a day reduced HSV-1 titer in tear film, corneal tissue, and trigeminal ganglia. This animal model should be useful to conserve novel potential anti-viral drugs undergoing initial screening.

Acyclovir↗
PubMed1991

Exacerbation of inflammatory demyelinating polyneuropathy after bone marrow transplantation.

Two patients with hematologic malignancy and quiescent inflammatory demyelinating polyneuropathy developed severe exacerbations of polyneuropathy at the time of bone marrow transplantation. The clinical course in both patients was progressive despite therapy with immuno-suppressive agents, plasmapheresis, and high dose immunoglobulin. The polyneuropathy resulted in quadriplegia which contributed to the patients' deaths 175 and 48 days after transplantation. Sections of multiple peripheral nerves sampled post mortem in the first case revealed prominent demyelination with heavy infiltration of macrophages and lymphocytes. Immunohistochemical studies demonstrated that most of the lymphocytes were of the CD8+, cytotoxic/suppressor cell class and that many of the Schwann cells expressed class II (HLA-DR) antigen. This report suggests that bone marrow transplantation can exacerbate inflammatory demyelinating polyneuropathy.

Adult↗
PubMed1988

A recombinant vaccinia virus expressing herpes simplex virus type 1 glycoprotein B induces cytotoxic T lymphocytes in mice.

Spleen cells from BALB/c (H-2d) mice vaccinated with vgB11, a recombinant vaccinia virus which expresses glycoprotein B (gB) of herpes simplex virus type 1 (HSV-1), lysed EMT6 (H-2d) target cells infected with vgB11 or with HSV-1 but did not lyse uninfected EMT6 cells or infected L-929 (H-2k) target cells. Unlabelled target cell competition of lysis showed that only syngeneic cells infected with vgB11 or HSV-1 inhibited lysis of radiolabelled HSV-1-infected targets. These results demonstrate that vgB11 induces H-2-restricted anti-HSV-1 cytotoxic T lymphocytes and that gB is the target antigen.

Animals↗
PubMed1987

Expression of herpes simplex virus 1 glycoprotein B by a recombinant vaccinia virus and protection of mice against lethal herpes simplex virus 1 infection.

The herpes simplex virus 1 (HSV-1) strain F gene encoding glycoprotein gB was isolated and modified at the 5' end by in vitro oligonucleotide-directed mutagenesis. The modified gB gene was inserted into the vaccinia virus genome and expressed under the control of a vaccinia virus promoter. The mature gB glycoprotein produced by the vaccinia virus recombinant was glycosylated, was expressed at the cell surface, and was indistinguishable from authentic HSV-1 gB in terms of electrophoretic mobility. Mice immunized intradermally with the recombinant vaccinia virus produced gB-specific neutralizing antibodies and were resistant to a lethal HSV-1 challenge.

Animals↗
PubMed1984

Immunocytochemical localization of herpes simplex virus antigen in the trigeminal ganglia of experimentally infected mice.

The peroxidase anti-peroxidase (PAP) technique was used to study the distribution of herpes simplex virus (HSV) antigens in mouse ganglia during the acute infection and the transition into the latent infection. At 2 days after HSV inoculation by the corneal route, immunoperoxidase staining was present in occasional isolated neurons of the trigeminal ganglion and also in scattered satellite cells. By 4 days, more cells were stained with the infection centered in the medial portion of the ganglion. Inflammatory cells were present around PAP-labeled fragments from lysed cells. Stained satellite cells often with a hypertrophic appearance surrounded labeled or unlabeled neurons in a ring-like array. At 6 days after HSV inoculation, there was a decrease both in the number of cells stained and in the intensity of staining. By 8 days, HSV antigens could be detected by weak PAP staining only in neurons. Otherwise, these neurons appeared morphologically normal. No immunoperoxidase staining was present after the 8th day. These results are compatible with retrograde axoplasmic transport of HSV and cell to cell spread of virus in ganglia. Also the appearance of infected ganglion cells during the transition to latency suggests that neurons can be switched from an HSV-permissive to a non-permissive (latent) state.

Animals↗
PubMed1984

Different sizes of restriction endonuclease fragments from the terminal repetitions of the herpes simplex virus type 1 genome latent in trigeminal ganglia of mice.

Trigeminal ganglion DNA from mice latently infected with herpes simplex virus type 1 was analysed by restriction enzyme digestion, agarose gel electrophoresis and blot hybridization to 32P-labelled viral DNA. Viral DNA from parental virions and from virions obtained as a consequence of reactivation by ganglion neurectomy were similarly analysed. The BamHI restriction fragments of parental and reactivated virions were almost indistinguishable from each other, and several of the larger BamHI fragments of viral DNA were also found in latently infected ganglion at unaltered sizes. In contrast, fractionation of EcoRI fragments of latently infected ganglion DNA by reverse phase column (RPC-5) chromatography, followed by gel electrophoresis and blot hybridization to a viral DNA probe from the S component terminal repetition, revealed the presence of several terminal fragments at discrete sizes ranging from 1 kb to 15 kb, quite unlike the 5.7 kb terminal EcoRI K fragment of virion-derived DNA. These results indicate that structural changes occur in the viral genome concomitantly with the establishment of latency, such as may result from extensive gene rearrangement or integration into cellular DNA.

Animals↗
PubMed1984

Encephalitis resulting from reactivation of latent herpes simplex virus in mice.

Herpes simplex virus (HSV) encephalitis was produced in mice from reactivation of latent virus. Two experimental models were used: the trigeminal model after corneal inoculation of HSV, and the hypoglossal model after tongue inoculation of HSV. In the trigeminal model, cyclophosphamide treatment induced reactivation of latent virus in ganglia but not in central nervous system tissue. Spread of the reactivated virus from ganglia to brain occurred only in mice deficient in anti-HSV antibody. In the hypoglossal model, sectioning of the hypoglossal nerve provoked chromatolysis in the corresponding central nervous system motor neurons and occasionally reactivated latent HSV in the brains of mice. These results suggest that HSV encephalitis can result from the spread of reactivated virus from ganglia to brain and also from in situ reactivation in brain.

Animals↗
PubMed1983

Latency of herpes simplex virus in ocular tissue of mice.

At 5 to 7 months after corneal inoculation of herpes simplex virus type 1 in mice, explants of ocular tissue yielded virus. Immunoperoxidase study of explants undergoing reactivation revealed herpes simplex virus antigens in retinal tissue. These results indicate that herpes simplex virus can establish and maintain latency in ocular tissue, most probably in the retina.

Animals↗